In search of models for accelerated aging, skin samples and cultures of fibroblasts and keratinocytes will be obtained from persons who exhibit features of premature cutaneous senescence, including xeroderma pigmentosum and dyskeratosis congenita. Patients with psoriasis, receiving 8-methoxypsoralen and UV light (PUVA) will be studied sequentially. We will measure parameters of cell growth; capacity for DNA repair of thymine dimers and psoralen cross-links; and sister-chromatid exchanges. In cultured cells from PUVA patients we will study rates of collagen biosynthesis and degradation by measuring prolyl hydroxylase, different genetic types of collagen and collagenase activity. Type specific proteins of epidermis (the keratin peptides) will be purified and peptide fragments examined for sequence homologies. Trypsin and cyanogen bromide fragments will be analysed. Fibroblasts and keratinocytes will be examined for their ability to transport putrescine. The influence of insulin and epidermal growth factor on polyamine transport and ornithine decarboxylase will be measured. The objectives of the ultrastructural portion of this project are to evaluate possible changes in: (1) the dermal vasculature in relation to the formation of telangiectases and senile purpura; (2) elastin, collagen and fibroblasts in relation to the development of elastosis; and (3) epidermal cells in relation to the development of skin cancer.